Dynorphin inhibits NEP activity in R1.1 mouse thymoma cells.
NEP/CALLA or CD10 is an endopeptidase (E.C. 3.4.24.11) that inactivates numerous neuropeptides, including dynorphin. Dynorphin is an endogenous opioid polypeptide that binds to kappa-opioid receptors with greatest affinity. R1.1 mouse thymoma cells highly express kappa-opioid receptors. In this study, on R1.1 cells, NEP activity was inhibited by kappa-opioid polypeptide dynorphin (10(-8)-10(-6) M) and by thiorphan (2 x 10(-4) M), a known inhibitor of NEP (30 min treatment). NEP inhibition by dynorphin was stronger than by thiorphan. A non-opioid opioid mechanism of action was mostly involved in this inhibition.
Martin-Kleiner
Irena
I
Division of Molecular Medicine, Ruder Bosković Institute, Zagreb, Croatia. kleiner@irb.hr
Balog
Tihomir
T
Marotti
Tanja
T
D000818:Animals; D045744:Cell Line, Tumor; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D015260:Neprilysin / Q000096:biosynthesis / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology; D013945:Thymoma; D013953:Thymus Neoplasms
D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D013876:Thiophenes; C045141:thiophane; C051844:norbinaltorphimine; D009271:Naltrexone; D004399:Dynorphins; D015260:Neprilysin